Potato carboxypeptidase inhibitor (PCI) is a naturally occurring
protease inhibitor peptide in
potatoes
The potato is a starchy food, a tuber of the plant ''Solanum tuberosum'' and is a root vegetable native to the Americas. The plant is a perennial in the nightshade family Solanaceae.
Wild potato species can be found from the southern United ...
that can form complexes with several
metallo-carboxypeptidases,
inhibiting them in a strong
competitive way with a
Ki in the nanomolar range.
PCI consists of 39 amino acids (
MW 4295
Da) forming a 27-residue globular core stabilized by three
disulfide bridges and a
C-terminal tail with residues 35–39. PCI contains a small
cysteine
Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile.
When present as a deprotonated catalytic residue, sometime ...
-rich module, called a
T-knot scaffold, that is shared by several different protein families, including the
EGF EGF may refer to:
* E.G.F., a Gabonese company
* East Grand Forks, Minnesota, a city
* East Garforth railway station in England
* Epidermal growth factor
* Equity Group Foundation, a Kenyan charity
* European Gendarmerie Force, a military unit of ...
family.
Medicinal properties
Because of the structural similarities with EGF, PCI inhibits
tumor cell growth.
Mechanism of action is inhibition of receptor dimerization and receptor
trans-autophosphorylation induced by epidermal growth factor (EGF). PCI blocks the formation and activation of
ErbB1/
ErbB-2
Receptor tyrosine-protein kinase erbB-2 is a protein that in humans is encoded by the ''ERBB2'' gene. ERBB is abbreviated from erythroblastic oncogene B, a gene originally isolated from the avian genome. The human protein is also frequently refer ...
(EGFR and HER2)
heterodimer
In biochemistry, a protein dimer is a macromolecular complex formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ''dimer'' has ...
s that have a prominent role in
carcinoma
Carcinoma is a malignancy that develops from epithelial cells. Specifically, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that arises from cells originating in the endodermal, mesodermal ...
development.
PCI also inhibits
transforming growth factor alpha
Transforming growth factor alpha (TGF-α) is a protein that in humans is encoded by the TGFA gene. As a member of the epidermal growth factor (EGF) family, TGF-α is a mitogenic polypeptide. The protein becomes activated when binding to receptors c ...
(TGF-alpha).
In addition for pancreatic enzymes
carboxypeptidase A and B, PCI also inhibits carboxypeptidase R without affecting the activity of carboxypeptidase N in the circulation and have therefore use in
thrombolytic therapy (
blood clot lysis).
References
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Further reading
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See also
Scaffold (disambiguation)
A scaffold, or scaffolding, in construction, is a temporary structure that supports workers and equipment above the ground or floor.
Scaffold and scaffolding may also refer to:
Structures
* Scaffold (execution site), a raised, stage-like site fo ...
Protein kinase
Chemotherapy
Thrombolysis
Cancer research
{{DEFAULTSORT:Potato Carboxypeptidase Inhibitor
Protease inhibitors